ENKEPHALINASE INHIBITOR POTENTIATES MAMMALIAN TACHYKININ-INDUCED CONTRACTION IN FERRET TRACHEA

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  • 1 December 1987
    • journal article
    • research article
    • Vol. 243  (3) , 1211-1217
Abstract
To determine the roles of endogenous enkephalinase (EC.3.4.24.11) in regulating tachykinin-induced contraction of airway smooth muscle, the authors studied the effects of the enkephalinase inhibitor leucine-thiorphan on the contractile responses to substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) in isolated ferret tracheal smooth muscle segments. Leucine-thiorphan shifted, in concentration-dependent fashions, the dose-response curves to all tachykinins to lower concentrations. Leucine-thiorphan changed the rank order of tachykinin potency from NKA > SP > NKB to NKA = NKB > SP. Removal of the epithelium slightly enhanced the contractile responses to SP and NKA but not to NKB. Atropine shifted the dose-response curves of all tachykinins to higher concentrations. Each tachykinin increased the contractile response to electrical field stimulation (5 Hz, 20 sec of duration, 20 V) in a dose-dependent fashion. This effect was not altered by hexamethonium, indomethacin, BW755C or naloxone but was potentiated by leucine-thiorphan and inhibited by the tachkinin receptor antagonist (D-Pro2, D-Trp7.9)-SP and by atropine. Because tachykinins did not affect contractile responses to acetylcohline significantly, their effects were probably on presynaptic postganglionic nerves. Captopril, bestatin and leupeptin did not alter contractile responses, suggesting that angiotensin converting enzyme, aminopeptidases and serine proteinase did not modulate tachykinin-induced effects. Enkephalinase immunofluorescene was found in the smooth muscle and epithelium and confirmed the authors'' finding of enkephalinase-like activity in the muscle. The results suggest that tracheal enkephalinase is an important modulator of tachykinin-induced effects.

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